Abstract

Abstract Study question To compare the division timings and morphikinetic top-quality embryo rates derived from GnRH-antagonist ICSI cycles triggered with either hCG, GnRH-agonist or Dual trigger. Summary answer GnRH-agonist trigger derived embryos had significantly shorter division timing durations and a higher top-quality cleavage embryo rates compared to the other trigger groups What is known already TMS allows embryo quality assessment by documenting timing of events and length of intervals in embryo development, providing a more objective scoring of the embryos for embryo selection. Developing an in-house model for embryo selection based on Known Implantation Data (KID) embryos enables detecting the top-quality embryos selected for transfer. It remains to be determined what factors influence oocyte maturation, embryo kinetics and the developmental potential and quality of the embryos obtained. We sought to evaluate if the rate of optimal timed top-quality embryos is influenced by the type of triggering in GnRH-antagonist ICSI cycles. Study design, size, duration Top quality embryo rates and outcome of embryos derived from GnRH- antagonist ICSI cycles triggered by hCG (Ovitrelle 250mcg), GnRH-agonist (Decapaptyl 0.2MG) and dual trigger (co- administration of GnRH-agonist and hCG) between July 2013 - December 2020 were compared. Top- quality embryos with the highest chance to implant were defined : tPNf <24.08, t2<26.6, S2<0.9 and t8<56 hours post insemination (hPi) for cleavage embryos and t2<26.6, S2<0.9, t8<56 and tSB<96.6 hPi for blastocysts. Participants/materials, setting, methods Optimal time durations: time to polar body extrusion (tPB2), time to pronucleus fading (tPNf), cleavage timings (t2-t8), synchrony of the second and third cycles (S2 and S3), duration of the second cycle (CC2) time to start blastulation (tSB) were set based on an in-house model including embryos with known implantation data. Multivariate logistic regression analysis age, type of gonadotrophins, number of oocytes aspirated and peak estradiol levels was performed. Pregnancy rates were calculated from transfers. Main results and the role of chance We analyzed 3,352 embryos derived from 1162 GnRH-antagonist ICSI cycles; 2,169 embryos in the hCG trigger group, 737 embryos in the GnRH-agonist group and 446 embryos in the Dual trigger group. The groups were similar in demographic characteristics apart for a higher maternal age with Dual trigger and higher gravidity with hCG. As for treatment parameters the groups were similar in dose of gonadotrophins, peak estradiol levels and endometrial thickness; however differed in number of oocytes aspirated - highest with GnRH-agonist (Decapeptyl 0.2mg) trigger and maturation rate - highest with hCG. Division timing durations (tPB2, tPNf, t2-t7) were significantly shorter in the GnRH-agonist group compared to the other groups. The highest top quality cleavage embryo rate was with GnRH-agonist trigger compared to hCG and Dual trigger (21.6% versus 12.7% and 20.2% respectively, p < 0.001). Pregnancy rates were similar between the groups. In the multivariate regression model assessing cell cycle divisions parameters and top quality cleavage rates; the type of trigger remained a significant factor after controlling for age, type of gonadotrophins, number of oocytes aspirated and peak estradiol levels. Limitations, reasons for caution The strengths are a single center study with embryos cultured under the same standardized laboratory conditions. GnRH-antagonist ICSI cycles were included to standardize the protocol and control for fertilization time. The retrospective nature of the study is a limitation. Wider implications of the findings Developing an in-house model an important additive tool for improving embryo selection for transfer. It enables the classification of embryo quality according to morphokinetic parameters. Finding treatment parameters that influence morphokinetic embryo quality may be of importance in IVF success rates. Trial registration number not applicable

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